α-Alkyl-α-amino acids represented by the formula H2NCH(R)COOH are very important naturally occurring amino acids. Most of the α-alkyl-α-amino acids exist in animals, plants, microorganisms or the like in the L-form having a L-configuration at a position carbon, and the L-form constitutes a polypeptide chain. On the other hand, the D-form exists in plants, fungi or microorganisms as a non-protein compound. Furthermore, α,α-dialkyl-α-amino acids represented by a formula H2NC(R)(R′)COOH are compounds that are recently gaining attention because of their unique functions such as being stereochemically stable and being not susceptible to enzymatic hydrolysis by protease when the compound is incorporated into a peptide. Regarding the above-described respects, see Bellier, B, et al., J. Med. Chem., vol. 40, p. 3947, 1997; and Mossel, E. et al., Tetrahedron Asymmetry, vol. 8, p. 1305, 1997. The compounds can be used, for example, as peptides having an enhanced activity, effective enzyme inhibitors, and chiral building blocks for synthesizing compounds having various biological activities. Such α,α-dialkyl-α-amino acids have been examined to be prepared by catalystic asymmetric reaction, but at present, no effective method for preparing the same has been found out.
For example, the significance of chiral phase-transfer catalysts, which allow stereoselective alkylation of glycine derivatives, is increased in the field of process chemistry because of its easy application. A large number of researches as to design of phase-transfer catalysts have been conducted by using mainly cinchona alkaloid derivatives until now and several useful methods have been reported (e.g., see Shioiri, T. et al., Stimulating Concepts in Chemistry, edited by Vogtle, F. et al., WILEY-VCH: Weinheim, p. 123, 2000; and O'Donnell, M. J., Aldrichimica Acta, vol. 34, p. 3, 2001). However, when such phase-transfer catalysts are used, various problems are caused such as use of a halogen-based solvent, a long time reaction, or the necessity of low temperature conditions. In particular, for synthesizing α,α-dialkyl-α-amino acids as described above, chiral phase-transfer catalysts derived from such cinchona alkaloid are not very useful.
The present inventors have prepared an optically active quaternary ammonium salt having axial asymmetry, and clarified that it can be used as a phase-transfer catalyst for synthesizing stereoselectively α-amino acids as described above (see Japanese Laid-Open Patent Publication No. 2001-48866; Japanese Laid-Open Patent Publication No. 2003-81976; and Ooi, T. et al., J. Am. Chem. Soc., vol. 122, p. 5228, 2000). For example, a spiro-compound represented by the following formula is very useful for asymmetric double alkylation of glycine derivatives and asymmetric monoalkylation of α-alkyl-α-amino acid derivatives (e.g., alanine derivatives):
(where PhF3 represents 3,4,5-trifluorophenyl group). However, a large number of processes are required in order to prepare such spiro catalysts, and for example, when chiral binaphthol, which is easily available, is used as the starting raw material, as many as eleven processes are required only to prepare the structural portion on the left side of the catalyst. Thus, preparation takes time and labor, and results in high cost, which are large drawbacks.